Aphton Corporation

Cancer Advances, Inc.

Receptor Biologix, Inc.

Stephen Grimes

Stephen L Karr

Philip C Gevas

Richard L Littenberg

Robert J Scibienski

Dov Michaeli

Elizer Benjamini

Susan A Watson

Martyn Caplin

John Little

Lorraine McLoughlin

Vernon C Stevens

Lorraine Mcloughlin

Ronald Makishima

The present invention provides progastrin-binding molecules that are useful therapeutically for passive immunization against progastrin in gastrin-promoted diseases or conditions. The progastrin-binding molecules are specific for progastrin but do not bind gastrin-17(G17), gastrin-34(G34), glycine-extended gastrin-17(G17-Gly) or glycine-extended gastrin-34(G34-Gly). The progastrin-binding molecules include monoclonal antibodies (MAbs) selective for sequences at the N-terminus and the C-terminus of the gastrin precursor molecule, progastrin.

Monoclonal antibodies to progastrin

A combination for use in the treatment of pancreatic cancer comprising:

Combination treatment of pancreatic cancer

The present invention relates to a combination therapy method for treating gastrin-dependent tumors. The method comprises the immunization of a patient with an anti-gastrin 17 immunogenic composition in combination with the administration of chemotherapeutic agents such as 5-fluorouracil and leucovorin.

Combination therapy for the treatment of tumors

The present invention provides progastrin-binding molecules specific for progastrin that do not bind gastrin-17(G17), gastrin-34(G34), glycine-extended gastrin-17(G17-Gly), or glycine-extended gastrin-34(G34-Gly). Further, the invention provides monoclonal antibodies (MAbs) selective for sequences at the N-terminus and the C-terminus of the gastrin precursor molecule, progastrin and the hybridomas that produce these MAbs. Also provided are panels of Mabs useful for the detection and quantitation of progastrin and gastrin hormone species in immuno-detection and quantitation assays. These assays are useful for diagnosing and monitoring a gastrin-promoted disease or condition, or for monitoring the progress of a course of therapy. The invention further provides solid phase assays including immunohistochemical (IHC) and immunofluorescence (IF) assays suitable for detection and visualization of gastrin species in solid samples, such as biopsy samples or tissue slices. The progastrin-binding molecules are useful therapeutically for passive immunization against progastrin in progastrin-promoted diseases or conditions. Also provided are surrogate reference standard (SRS) molecules that are peptide chains of from about 10 to about 35 amino acids, wherein the SRS molecule comprises at least two epitopes found in a protein of interest of greater than about 50 amino acids. Such SRS molecules are useful as standards in place of authentic proteins of interest.

The invention provides assay methods for the detection and quantitation of gastrin hormones, including total and free gastrin hormone in a sample. ELISA-type heterogeneous phase assays suitable for use with biological fluid samples such as blood, plasma or other bodily fluids of a mammal, particularly a human subject are provided. The method provides a precise assay for the amounts of free and total G17 and G34 in biological fluid samples, as well as the amounts of free and total Gly-extended G17, and Gly-extended G34. Also provided are methods of determining suitable treatment for patient suffering from a gastrin hormone-mediated disease or condition employing gastrin hormone immunoassays.

Gastrin hormone immunoassays

Immmunogenic compositions useful for the treatment of ulcers or tumors whose growth is dependent on or stimulated by gastrin hormones are disclosed. The immunogenic compositions induce antibodies in a subject which selectively neutralize the specific hormones. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are disclosed. A method of reversing the inventive treatments by neutralizing the antibodies induced in vivo is also disclosed.

Immunogenic compositions against gastrin peptides

Chimeric peptide epitopes can serve as effective immunogens against hormones and other small peptides or proteins. Thus, immunogenic peptides are selected from promiscuous Th epitopes and synthesized together with self antigenic peptide sequences fused with or without end to end spacer peptide interconnections. A peptide sequence which may be of the gonadotropin releasing hormone is linked with an immunogenic peptide sequence selected from a promiscuous Th-epitope of measles virus protein F, tetanus toxoid, or malaria protein CSP. Compositions of the chimeric immunogen are found effective in eliciting high and specific anti-GnRH antibody titers.

Chimeric peptide immunogens

The invention concerns immunogens, immunogenic compositions and method for the treatment of gastrin-dependent tumors. The immunogens comprise a peptide from the CCK-B/gastrin-receptor conjugated to a spacer and to an immunogenic carrier. The immunogens are capable of inducing antibodies in vivo which bind to the CCK-B/gastrin-receptor in tumor cells, thereby preventing growth stimulating peptide hormones from binding to the receptors, and inhibiting tumor cell growth. The immunogens also comprise antibodies against the CCK-B/gastrin-receptor for passive immunization. The invention also concerns diagnostic methods for detecting gastrin-dependent tumors in vivo or from a tissue biopsy using the antibodies of the invention.

Immunogenic compositions to the CCK-B/gastrin receptor and methods for the treatment of tumors

A system is described for conjugating, isolating, and purifying proteins. The system contains an ultrafiltration apparatus which is connected with a reaction vessel reservoir.

System for method for the modification and purification of proteins

Immunogenic compositions capable of generating an immune response in mammals against GnRH are disclosed. The immunogenic compositions are effective in methods of treating gonadotropin and gonadal steroid hormone dependent diseases and immunological contraception of mammals.

Methods for the treatment of hormone-dependent tumors with immunogens against gonadotropin releasing hormone

Immunogens against gonadotropin releasing hormone

Immunogenic compositions useful for the treatment or prevention of gastric or duodenal ulcer disease are disclosed. The immunogenic compositions effectively operate by inducing antibodies in a subject which selectively neutralize specific peptide gastric hormones and inhibit the binding of the hormones to physiological receptors thus limiting the secretion of stomach acid. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are also disclosed.

Method for the treatment and prevention of gastric and duodenal ulcer

Immunogenic compositions useful for the treatment of ulcers or tumors whose growth is dependent on or stimulated by gastrin hormones are disclosed. The immunogenic compositions induce antibodies in a subject which selectively neutralize the specific hormones. Pharmaceutical compositions comprising effective amounts of the immunogenic compositions and methods of treatment using the compositions are disclosed. A method of reversing the inventive treatments by neutralizing the antibodies induced in vivo is also disclosed.

Growing community of inventors

Davis, CA, United States of America

Stephen Grimes